Arachidonate and medium-chain fatty acids inhibit transcription of the acetyl-CoA carboxylase gene in hepatocytes in culture.
Transcription of acetyl-CoA carboxylase in avian liver is low during starvation or after consumption of a low-carbohydrate, high-fat diet and high during consumption of a high-carbohydrate, low-fat diet. The role of fatty acids or metabolites derived from fatty acids in the nutritional control of acetyl-CoA carboxylase transcription was investigated by determining the effects of long- and medium-chain fatty acids on acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes. Palmitate, oleate, and arachidonate caused a decrease in acetyl-CoA carboxylase activity in hepatocytes incubated with triiodothyronine (T3). The inhibition of acetyl-CoA carboxylase activity caused by arachidonate was accompanied by a similar decrease in transcription of the acetyl-CoA carboxylase gene. In contrast, neither palmitate nor oleate were effective in modulating acetyl-CoA carboxylase transcription. These results are consistent with arachidonate or a metabolite derived therefrom mediating the effects of diets containing high levels of n-6 polyunsaturated fatty acids on acetyl-CoA carboxylase transcription in liver. Hexanoate and octanoate also inhibited acetyl-CoA carboxylase activity in the presence of T3. The magnitude of the hexanoate- or octanoate-induced decrease in acetyl-CoA carboxylase activity was greater than that observed for long-chain fatty acids. Hexanoate and octanoate inhibited acetyl-CoA carboxylase activity at a transcriptional step, and did so within 2 h of addition of fatty acid. Addition of carnitine partially reversed the inhibitory effects of octanoate on acetyl-CoA carboxylase expression, suggesting that a metabolite of octanoate is involved in mediating this response. 2-Bromooctanoate was a more potent inhibitor of acetyl-CoA carboxylase expression than octanoate or hexanoate. We postulate that a metabolite of hexanoate and octanoate, possibly a six or eight carbon acyl-CoA, plays a role in the nutritional regulation of acetyl-CoA carboxylase transcription.
Hillgartner
F B
FB
Department of Biochemistry, School of Medicine, West Virginia University, Morgantown 26506, USA.
Charron
T
T
D000103:Acetyl-CoA Carboxylase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D015152:Blotting, Northern; D002210:Caprylates / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D002642:Chick Embryo; D005227:Fatty Acids / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D002210:Caprylates; D005227:Fatty Acids; D012333:RNA, Messenger; D014284:Triiodothyronine; D016718:Arachidonic Acid; D000103:Acetyl-CoA Carboxylase; C031492:octanoic acid